Bioinformatic analyses reveal lysosomal-associated protein transmembrane 5 as a potential therapeutic target in lipotoxicity-induced injury in diabetic kidney disease

Abstract

Emerging data have revealed that damage to tubular epithelial cell is a driving force in the progression of diabetic kidney disease (DKD). However, the specific mechanisms by which lipotoxicity contributes to the injury of these cells, thereby influencing the development of DKD, are yet to be fully understood. Here, we analyzed the GSE 30529 microarray datasets of human tubulointerstitial tissue samples from the Gene Expression Omnibus database (GEO). Concurrently, we conducted RNA-sequencing on palmitic acid (PA)-treated human renal proximal tubule epithelial cells (HK2 cells). After normalization, the differentially expressed genes (DEGs) were screened by R software and gene ontology (GO) enrichment analysis was conducted, and lysosomal-associated protein transmembrane 5 (LAPTM5) was finally selected. Our findings indicate that the expression of LAPTM5 was obviously increased in DKD patients, and the correlation between LAPTM5, and other clinical parameters of DKD was analyzed using the Spearman correlation analysis. The potential of LAPTM5 as a prognostic biomarker for DKD was further consolidated through receiver operating characteristic (ROC) analysis. To further verify the function of LAPTM5, we established mouse or in vitro systems mimicking DKD. The results showed that a consistent upregulation of LAPTM5, which was also found to be linked with inflammatory mediators within the context of DKD. Additionally, LAPTM5 silencing significantly downregulated mRNA expression of inflammatory factors in PA-treated HK2 cells. These results indicate that LAPTM5 is a potential biomarker and therapeutic treatment target for DKD. This discovery paves the way for future research and development of targeted interventions aimed at mitigating the progression of this prevalent condition.

Keywords:

• Diabetic kidney disease
• biomarker
• lipotoxicity
• LAPTM5
• bioinformatics
• inflammation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Data curation, Ciyou Huang and Jiayi Liu; Formal analysis, Xin Chen, Shenglong Zhu, Jiayi Liu and Jinbang Wang; Funding acquisition, Siyuan Cui; Investigation, Jiayi Liu; Methodology, Xin Chen and Shenglong Zhu; Project administration, Siyuan Cui; Resources, Ciyou Huang; Software, Xin Chen; Supervision, Siyuan Cui; Visualization, Shenglong Zhu; Writing–original draft, Jinbang Wang; Writing–review & editing, Ciyou Huang.

Ethics approval

The study protocol was approved by the Institutional Animal Care and Use Committee of the Medical School of Jiangnan University (approval number: JN. No 20220315c0301001[079]).

Consent for publication

Not applicable.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (grant No.82000685), Jiangsu Provincial Association for Science and Technology Youth Science and Technology Talent Support Project (grant No. JSTJ-2023-WJ003), Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (grant No.BJ2023034), and Modern Industry Development Fund Project of Wuxi Science and Technology Bureau (grant No. K20231059). The funders had no roles in the design of the study and collection, analysis, and interpretation of data or in writing the manuscript.